Effect of the Inhibition of the Mammalian Target of Rapamycin on Metabolism and Exercise

Muscle Strength Clinical Trial

— EXETOR  

Official title:

Effect of the Inhibition of the Mammalian Target of Rapamycin on Metabolism and Exercise.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01561404
• Other study ID #: MTOR-METAB
• Secondary ID: 2009-010541-31
• Status: Terminated
• Phase: Phase 4
• First received: March 20, 2012
• Last updated: April 27, 2015
• Start date: September 2011
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

This is an exploratory study based on the hypothesis that kidney transplant patients treated with an immunosuppressive therapy based on an inhibitor of the mammalian target of rapamycin (m-TOR) may increase resistance to physical exercise, which would result in an improvement in the quality of life of these patients.

Description:

The hypothesis of the present study is that, with respect to calcineurin inhibitors, the mTOR inhibitor-based immunosuppression may alter the physical exercise capacity in renal transplant patients.

This is based on recent data obtained. Regarding metabolism there is evidence that inhibition of mTOR, reduces muscle glucose utilization, as well as, increase fatty acid oxidation. On the other hand, has shown that drugs based on mTOR inhibitors in the context of excess of nutrients improves intracellular glucose uptake in skeletal muscle cells. Through these mechanisms could increase resistance to physical exercise, which would result in an improvement in the quality of life of patients. Nevertheless, there isn't any paper that has explored this hypothesis accurately.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Renal transplant patient's aged between 18 and 60 years old.

2. Heart rate in radial pulse and seated between 50 and 100 bpm.

3. Systolic blood pressure between 100 and 140 and diastolic between 50 to 90.

4. Absence of any clinical physical, psychological or psychiatric condition that would prevent from the protocol described follow-up.

5. Estimated glomerular filtration rate greater than 40 ml / min.

6. Proteinuria < 0.5 g / d.

7. Renal transplantation at least 6 months ago.

8. Immunosuppressant based on calcineurin inhibitors.

9. Hemoglobin > 11 g / dl.

10. Body mass index (BMI) < 35 kg/m2.

11. Indication for conversion to everolimus and granting of written informed consent.

Exclusion Criteria:

1. Diabetes mellitus

2. Treatment with erythropoiesis stimulating drugs

3. Treatment with ß blockers drugs

4. Participation in any clinical trial in the last 30 days prior to the inclusion.

5. Any other physical illness, psychological or psychiatric condition that could difficult the follow-up of the patient.

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Disorder Related to Renal Transplantation
• Exercise, Aerobic
• Muscle Strength

Intervention

Drug:
• Everolimus
In patients that change of immunosuppressive therapy from calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) to m-TOR (everolimus)has been clinically indicated, check if there is an increase in physical exercise capacity.

Locations

Country	Name	City	State
Spain	Nephrology Department. Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelone

Sponsors (1)

Lead Sponsor	Collaborator
Josep M Cruzado

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscular strength	The principal variable is the increase of the exercise capacity measured by 2 sub-varibles: muscular strenght and decrease of oxygen consumption in the tissues.	Change from baseline to 6-8 weeks after m-TOR conversion	No
Primary	Oxygen consumption in the tissues	The principal variable is the increase of the exercise capacity measured by 2 sub-varibles: muscular strenght and decrease of oxygen consumption in the tissues.	Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Anthropometric measures	Measure of anthropometric measures including height,weight, muscular folds( biceps, triceps, subscapular, pectoral, axillary, abdominal, suprailiac, thigh and leg) and perimeters (arm, forearm, wrist, abdominal, waist, hip, thigh, groin, thigh and leg).	Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Strength of the hand	Measure of the strenght of the hand will include:test of maximum strength of contraction of the palm, maximum resistance force of the palm and maximum power on a cycle ergometer for 5 seconds with a constant resistance of 50 N.	Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Metabolic parameters- Cardioventilatory response	Cardioventilatory response measured with respiratory rate, ventilation, oxygen consumption, carbon dioxide production, respiratory quotient and tidal volume during stress test.	Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Metabolic parameters- Biochemical response	Lactate and blood glucose levels after stress test	Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Glucose tolerance test		Change from baseline to 6-8 weeks after m-TOR conversion	No
Secondary	Blood pressure	Continuos blood preassure measure (24 hours) with a holter monitor device.	Change from baseline to 6-8 weeks after m-TOR conversion	No